Evidence map›Paper›PMID 32138745›Full record

ArticleFluids and barriers of the CNS2020

The pivotal role of micro-environmental cells in a human blood-brain barrier in vitro model of cerebral ischemia: functional and transcriptomic analysis.

Anna Gerhartl, Nadja Pracser, Alexandra Vladetic, Sabrina Hendrikx, Heinz-Peter Friedl, Winfried Neuhaus

Open access · goldAbstract read
In one paragraph

Article in Fluids and barriers of the CNS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 37 citations in OpenAlex.

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  12. HumanTissue barriers · 2024
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  16. 3D In Vitro Blood-Brain-Barrier Model for Investigating Barrier Insults.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 1 institution in 1 country.

Anna GerhartlCompetence Unit Molecular Diagnostics, Center Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Nadja PracserCompetence Unit Molecular Diagnostics, Center Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Alexandra VladeticCompetence Unit Molecular Diagnostics, Center Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Sabrina HendrikxCompetence Unit Molecular Diagnostics, Center Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Heinz-Peter FriedlCompetence Unit Molecular Diagnostics, Center Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria.
Winfried NeuhausCompetence Unit Molecular Diagnostics, Center Health and Bioresources, AIT-Austrian Institute of Technology GmbH, Giefinggasse 4, 1210, Vienna, Austria. winfried.neuhaus@ait.ac.at.ORCID http://orcid.org/0000-0002-6552-7183
Austrian Institute of Technology · AT

Funding

Stiftung zur Förderung der Erforschung von Ersatz- und Ergänzungsmethoden zur Einschränkung von Tierversuchen project 060
6 · The paper itself

Abstract

backgroundThe blood-brain barrier (BBB) is altered in several diseases of the central nervous system. For example, the breakdown of the BBB during cerebral ischemia in stroke or traumatic brain injury is a hallmark of the diseases' progression. This functional damage is one key event which is attempted to be mimicked in in vitro models. Recent studies showed the pivotal role of micro-environmental cells such as astrocytes for this barrier damage in mouse stroke in vitro models. The aim of this study was to evaluate the role of micro-environmental cells for the functional, paracellular breakdown in a human BBB cerebral ischemia in vitro model accompanied by a transcriptional analysis.

methodsTranswell models with human brain endothelial cell line hCMEC/D3 in mono-culture or co-culture with human primary astrocytes and pericytes or rat glioma cell line C6 were subjected to oxygen/glucose deprivation (OGD). Changes of transendothelial electrical resistance (TEER) and FITC-dextran 4000 permeability were recorded as measures for paracellular tightness. In addition, qPCR and high-throughput qPCR Barrier chips were applied to investigate the changes of the mRNA expression of 38 relevant, expressed barrier targets (tight junctions, ABC-transporters) by different treatments.

resultsIn contrast to the mono-culture, the co-cultivation with human primary astrocytes/pericytes or glioma C6 cells resulted in a significantly increased paracellular permeability after 5 h OGD. This indicated the pivotal role of micro-environmental cells for BBB breakdown in the human model. Hierarchical cluster analysis of qPCR data revealed differently, but also commonly regulated clustered targets dependent on medium exchange, serum reduction, hydrocortisone addition and co-cultivations.

conclusionsThe co-cultivation with micro-environmental cells is necessary to achieve a functional breakdown of the BBB in the cerebral ischemia model within an in vivo relevant time window. Comprehensive studies by qPCR revealed that distinct expression clusters of barrier markers exist and that these are regulated by different treatments (even by growth medium change) indicating that controls for single cell culture manipulation steps are crucial to understand the observed effects properly.

Indexed as

Blood-Brain BarrierBrain IschemiaEndothelial CellsGene Expression ProfilingStrokeAnimalsCell Culture TechniquesCell LineCells, CulturedCoculture TechniquesHumansRatsBrain endothelial cellsCerebral ischemiaClaudinStrokeTraumatic brain injury

Identifiers

PMID32138745
PMCPMC7059670
OpenAlexW3010718787

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.